Wise Use of Antibiotics: Debunking Some Antibiotic Myths

Column Authors: Rana El Feghaly, MD, MSCI | Associate Chair, Ambulatory & Regional Quality Improvement, Department of Pediatrics; Director, Outpatient Antimicrobial Stewardship Program; Director, Infectious Diseases Clinical Services; Medical Director, Vaccines for Children (VFC) Program

Column Editor: Angela L. Myers, MD, MPH | Chief Wellbeing Officer

Antibiotics always seem to get certain reputations. Misconceptions continue to be perpetuated among the medical community, and it can be hard to know what is a myth and what is accurate. Let’s start the new year debunking some common myths in pediatric antibiotic stewardship!

Myth: Penicillin does not work on anything anymore!

A friend of mine was recently evaluated for streptococcal pharyngitis (not in KC!) and was prescribed cefdinir. When she asked why not penicillin, she was told, “Penicillin doesn’t work on anything anymore.” Although there is some truth to increasing penicillin resistance among many bacteria (Staphylococcus aureus is a good example where penicillin is almost never the answer anymore), some bacteria continue to be fully susceptible to penicillin: Streptococcus pyogenes (or Group A Streptococcus), and Streptococcus agalactiae (Group B Streptococcus) are two good examples. The Centers for Disease Control and Prevention tracks resistance for invasive cases and reports zero resistance to these two bacteria (https://www.cdc.gov/abcs/bact-facts/data-dashboard.html).

In fact, penicillin and amoxicillin are often superior to other broader antibiotics, not only because they are associated with fewer side effects, less cost or fewer alterations of the microbiome, but also, because of superior efficacy. For example, as we discussed in a previous article, amoxicillin is better absorbed and less protein bound compared to cefdinir, and thus can achieve concentrations for the time needed to kill common bacteria better than cefdinir can for most infections.

Myth: I cannot use cephalosporins if my patient is allergic to penicillin.

Not only are the vast majority of penicillin allergy labels inaccurate,^3,4 even in patients truly allergic to penicillin, most cephalosporins are safe. When a child has a type I hypersensitivity reaction (e.g., anaphylaxis, hives) to penicillin or amoxicillin, the allergy is generally to the side chain, and not the beta-lactam ring, which all beta lactams (penicillins, cephalosporins, carbapenems) share. The side chains are quite different in general, and cross-reactivity is exceedingly low. In our Outpatient Antibiotic Handbook, we now include an antibiotic allergy table that can help identify which cephalosporins are OK to administer to patients with true penicillin allergy. This applies to type I immediate hypersensitivity reactions. If a patient has developed a serious reaction such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), or serum sickness–like reaction, all beta-lactams should be avoided.

Myth: Doxycycline should not be used in children due to teeth staining.

In the 1960s, tetracycline use in young children who did not have their permanent teeth erupt yet resulted in a high prevalence of permanent teeth discoloration, since tetracycline can bind to calcium ions within teeth. Manufacturers advised against use of tetracycline and its derivatives, such as doxycycline, in children ≤8 years old due that concern. However, since then, we have discovered that doxycycline’s affinity to bind to calcium is much lower than tetracycline (19% for doxycycline compared to 39.5%-74.5% with tetracycline). Studies have failed to identify a significant risk for tooth discoloration when doxycycline is administered at standard doses and durations in pediatric patients.

Doxycycline is the drug of choice for most tickborne illnesses with no equivalent alternative and should be used regardless of the patient’s age when tickborne illnesses such as Rocky Mountain spotted fever or ehrlichiosis are considered.⁵

Myth: Fluoroquinolones should not be used in children.

I know many pediatric practitioners are weary of using fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, etc.). This resistance stems from concerns regarding cartilage toxicity raised shortly after approval of these drugs back in the ‘60s. Cartilage damage was observed in the weight-bearing joints of immature animals during testing back then. Additionally, in 2008, the U.S. Food and Drug Administration (FDA) released a boxed warning associating fluoroquinolone exposure with an increased risk of tendinitis and tendon rupture, particularly in the elderly. Multiple large pediatric studies have been performed since, and although they found a very slight increase in musculoskeletal adverse effects in children, most of those were reversible arthralgia, cartilage damage has not been observed, and fluoroquinolone-associated tendon rupture was extremely rare in children (<1 per million).

Fluoroquinolones have multiple additional boxed warnings including peripheral neuropathy, glucose dysregulation, neurological abnormalities and aortic dissection. They can cause QT prolongation and psychiatric complaints. They are not FDA approved in children yet. That being said, fluoroquinolones are the only oral antibiotics to treat Pseudomonas aeruginosa infections and may be preferred to avoid unnecessary IV therapy. Additionally, they may be needed for multidrug-resistant gram-negatives and resistant Streptococcus pneumoniae. Patients with severe (i.e., anaphylaxis) beta-lactam allergies may receive levofloxacin as an alternative treatment for pneumonia or sinusitis. It is important to only use fluoroquinolones when no alternative option exists, but we should not completely disregard these antibiotics when needed.⁶

If in doubt about an antibiotic, the Children’s Mercy Antibiotic Stewardship team is always happy to support. Email us at AntimicrobialStewards@cmh.edu.

References:

1. Gerber JS, Ross RK, Bryan M, et al. Association of broad- vs narrow-spectrum antibiotics with treatment failure, adverse events, and quality of life in children with acute respiratory tract infections. JAMA. 2017;318(23):2325-2336.
2. Vangay P, Ward T, Gerber JS, Knights D. Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe. 2015;17(5):553-564.
3. Jeimy S, Ben-Shoshan M, Abrams EM, et al. Practical guide for evaluation and management of beta-lactam allergy: position statement from the Canadian Society of Allergy and Clinical Immunology. Allergy Asthma Clin Immunol. 2020;16(1):95.
4. Khan DA, Banerji A, Blumenthal KG, et al. Drug allergy: A 2022 practice parameter update. J Allergy Clin Immunol. 2022;150(6):1333-1393.
5. Gaillard T, Briolant S, Madamet M, Pradines B. The end of a dogma: the safety of doxycycline use in young children for malaria treatment. Malar J. 2017;16(1):148.
6. El Feghaly RE, Goldman JL. Perceived harm may be helpful: fear of fluoroquinolone-associated adverse events in children. Pediatrics. 2021;147(6).